A molecular analysis of meropenem–vaborbactam non-susceptible KPC-producing Klebsiella pneumoniae

Antibacterial Resistance Leadership Group

doi:10.1128/aac.00208-24

A molecular analysis of meropenem–vaborbactam non-susceptible KPC-producing Klebsiella pneumoniae

Antibacterial Resistance Leadership Group

Pharmacy

Louis Stokes Cleveland VA Medical Center
Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
Case Western Reserve University
University of North Carolina at Chapel Hill
Duke University
University of California at San Francisco
Hackensack Meridian Health

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

We characterized the molecular determinants of meropenem–vaborbactam (MV) non-susceptibility among non-metallo-β-lactamase-producing KPC-Klebsiella pneumoniae (KPC-KP). Whole-genome sequencing was performed to identify mutations associated with MV non-susceptibility. Isolates with elevated MV MICs were found to have mutations encoding truncated or altered OmpK36 porins and increased bla_KPC copy numbers. KPC-KP isolates with decreased susceptibility to MV were detected among a collection of isolates predating the availability of MV.

Original language	English
Journal	Antimicrobial Agents and Chemotherapy
Volume	68
Issue number	10
DOIs	https://doi.org/10.1128/aac.00208-24
State	Published - Oct 2024

Keywords

Klebsiella pneumoniae carbapenemase
OmpK35
OmpK36
Vabomere resistance
antimicrobial resistance
meropenem
meropenem vaborbactam resistance
vaborbactam

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10.1128/aac.00208-24

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title = "A molecular analysis of meropenem–vaborbactam non-susceptible KPC-producing Klebsiella pneumoniae",

abstract = "We characterized the molecular determinants of meropenem–vaborbactam (MV) non-susceptibility among non-metallo-β-lactamase-producing KPC-Klebsiella pneumoniae (KPC-KP). Whole-genome sequencing was performed to identify mutations associated with MV non-susceptibility. Isolates with elevated MV MICs were found to have mutations encoding truncated or altered OmpK36 porins and increased blaKPC copy numbers. KPC-KP isolates with decreased susceptibility to MV were detected among a collection of isolates predating the availability of MV.",

keywords = "Klebsiella pneumoniae carbapenemase, OmpK35, OmpK36, Vabomere resistance, antimicrobial resistance, meropenem, meropenem vaborbactam resistance, vaborbactam",

author = "\{Antibacterial Resistance Leadership Group\} and Mohamad Yasmin and Marshall, \{Steven H.\} and Liang Chen and Rhoads, \{Daniel D.\} and Jacobs, \{Michael R.\} and Rojas, \{Laura J.\} and Federico Perez and Hujer, \{Andrea M.\} and Hujer, \{Kristine M.\} and \{van Duin\}, David and Vance Fowler and Chambers, \{Henry F.\} and Kreiswirth, \{Barry N.\} and Bonomo, \{Robert A.\}",

year = "2024",

month = oct,

doi = "10.1128/aac.00208-24",

language = "English",

volume = "68",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

number = "10",

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TY - JOUR

T1 - A molecular analysis of meropenem–vaborbactam non-susceptible KPC-producing Klebsiella pneumoniae

AU - Antibacterial Resistance Leadership Group

AU - Yasmin, Mohamad

AU - Marshall, Steven H.

AU - Chen, Liang

AU - Rhoads, Daniel D.

AU - Jacobs, Michael R.

AU - Rojas, Laura J.

AU - Perez, Federico

AU - Hujer, Andrea M.

AU - Hujer, Kristine M.

AU - van Duin, David

AU - Fowler, Vance

AU - Chambers, Henry F.

AU - Kreiswirth, Barry N.

AU - Bonomo, Robert A.

PY - 2024/10

Y1 - 2024/10

N2 - We characterized the molecular determinants of meropenem–vaborbactam (MV) non-susceptibility among non-metallo-β-lactamase-producing KPC-Klebsiella pneumoniae (KPC-KP). Whole-genome sequencing was performed to identify mutations associated with MV non-susceptibility. Isolates with elevated MV MICs were found to have mutations encoding truncated or altered OmpK36 porins and increased blaKPC copy numbers. KPC-KP isolates with decreased susceptibility to MV were detected among a collection of isolates predating the availability of MV.

AB - We characterized the molecular determinants of meropenem–vaborbactam (MV) non-susceptibility among non-metallo-β-lactamase-producing KPC-Klebsiella pneumoniae (KPC-KP). Whole-genome sequencing was performed to identify mutations associated with MV non-susceptibility. Isolates with elevated MV MICs were found to have mutations encoding truncated or altered OmpK36 porins and increased blaKPC copy numbers. KPC-KP isolates with decreased susceptibility to MV were detected among a collection of isolates predating the availability of MV.

KW - Klebsiella pneumoniae carbapenemase

KW - OmpK35

KW - OmpK36

KW - Vabomere resistance

KW - antimicrobial resistance

KW - meropenem

KW - meropenem vaborbactam resistance

KW - vaborbactam

UR - https://www.scopus.com/pages/publications/85206018474

U2 - 10.1128/aac.00208-24

DO - 10.1128/aac.00208-24

M3 - Article

C2 - 39162528

AN - SCOPUS:85206018474

SN - 0066-4804

VL - 68

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 10

ER -

A molecular analysis of meropenem–vaborbactam non-susceptible KPC-producing Klebsiella pneumoniae

Abstract

Keywords

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